Exhibit 10.1

     

    Confidential
Treatment Requested

     

    PUBLIC
HEALTH SERVICE

     

    SIXTH AMENDMENT TO
L-354-1998/0

     

    This is
the sixth amendment ("Sixth
Amendment") of the agreement by and between the National Institutes of
Health ("NIH") or the
Food and Drug Administration ("FDA"), hereinafter singly or
collectively referred to as agencies of the United States Public Health Service
("PHS") within the
Department of Health and Human Services ("HHS"), and Zonagen, Inc.
having an effective date of April 16,1999, and having NIH Reference Number
L-354-1998/0 ("Agreement").  This Sixth Amendment, having NIH Reference Number
L-354-1998/6, is made between the PHS through the Office of
Technology Transfer,
NIH, having an address at 6011 Executive Boulevard, Suite 325,
Rockville, Maryland 20852-3804, U.S.A., and Repros Therapeutics, Inc., having an
office at 2408 Timberloch Place, Suite B-7, The Woodlands, Texas 77280
("Licensee").  This Sixth Amendment includes, in
addition to the amendments made below, 1) a Signature Page and 2) Attachment 1
(Royalty Payment Information).

     

    WHEREAS, PHS and Licensee desire that the Agreement be amended a sixth
time as set forth below in order to change its Appendix B-Licensed
Fields-of-Use and Licensed Territory, Appendix C—Royalties, and
Appendix E-Benchmarks and Performance.

     

    NOW,
THEREFORE, in consideration of the mutual covenants and promises contained
herein, PHS and Licensee, intending to be
bound, hereby mutually agree to the following:

     

    
      	
              1) 

            	
              Replace
      Appendix B in theAgreement, as amended,
      with Appendix B as follows:

            


    

     

    Licensed
Fields-of-Use:  Treatment of human endocrinologic pathologies
or conditions in steroid-sensitive tissues, including cancers related to the
human reproductive system.

     

    Licensed Territory:
Worldwide.

     

    
      	
              2) 

            	
              Replace
      Appendix C, I.) (ii) c through g with the
  following:

            


    

     

    
      	
               
      

            	
              c.

            	
              [**]
      within thirty(30) days of filing the first New Drug Application for a
      Licensed Product
      with the United States FDA.

            


    

     

    
      	
               
      

            	
              d.

            	
              [**]
      within thirty(30) days of filing the first new drug application for a
      Licensed Product
      with the appropriate agency or regulatory body of any European
      country.

            


    

     

    
      	
               
      

            	
              e.

            	
              [**]
      within thirty(30) days of filing the first new drug application for a
      Licensed Product
      with the appropriate Agency or regulatory body in
  Japan.

            


    

     

    
      	
               
      

            	
              f.

            	
              [**]
      within thirty (30) days of receipt of the first marketing approval for a
      Licensed Product
      from the United States FDA.

            


    

     

    
      	
               
      

            	
              g.

            	
              [**]
      within thirty (30) days of receipt of the first marketing approval for a
      Licensed Product
      from the appropriate agency or regulatory body of any European
      country.

            


    

     

    
      	
               
      

            	
              h.

            	
              [**]
      within thirty (30) days of receipt of the first marketing approval for a
      Licensed Product
      from the appropriate agency or regulatory body in
  Japan.

            


    

     

    
      
        
          
            
              	
                      A-285-2009

                    	 
      	
                      CONFIDENTIAL

                    
	
                      Sixth
      Amendment of L-354-1998/0

                    	
                      Final
      REPROS THERAPEUTICS, INC.

                    	
                      July
      7, 2009

                    
	
                      Model
      09-2006 (updated 3-2009)

                    	
                      Page
      1 of 5

                    	
                      L-354-1998/6

                    


            

          

        

      

      


      __________________

      Portions
of this Exhibit have been omitted pursuant to a request for confidential
treatment pursuant to Rule 24b-2 under the Securities Exchange Act of 1934,
as amended, and Rule 406 under the Securities Act of 1933, as amended.
These omitted portions have been marked with "**" and have been filed separately
with the Securities and Exchange Commission.

    

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

    
       

      SIXTH AMENDMENT TO
L-354-1998/0

       

    

    
      	
              3)

            	
              Replace
      Appendix E in the Agreement, as amended, with Appendix E as
      follows:

            


    

     

    Licensee agrees to the
following Benchmarks for
the purpose of measuring its performance under this Agreement.
Licensee  shall notify  PHS  in
writing within thirty (30) days of achieving all such  Benchmarks.  They
are as follows:

     

    
      
        
          
            	 
      	
                    Benchmark

                  	 
      	
                    Date

                  
	
                    1.

                  	
                    Obtain
      financing, upfront licensing consideration, or any combination thereof
      (all of which are subject to section 1(vi) of Appendix C of
      this  Agreement ) of no less than a combined total of Six
      Million Dollars ($6,000,000)

                  	 
      	
                    9/30/2009

                  
	
                    2.

                  	
                    File
      NDA in U.S. for first indication

                  	 
      	
                    06/30/2011

                  
	
                    3.

                  	
                    File
      for approval of Licensed
      Product in Europe for first indication

                  	 
      	
                    [**]

                  
	
                    4.

                  	
                    File
      for approval of Licensed
      Product in Japan for first indication

                  	 
      	
                    [**]

                  
	
                    5.

                  	
                    Initiate
      Phase III clinical trial in U.S. for second indication

                  	 
      	
                    Completed

                  
	
                    6.

                  	
                    Initiate
      Phase III clinical trial in Europe for second indication

                  	 
      	
                    [**]

                  
	
                    7.

                  	
                    Initiate
      Phase III clinical trial in Japan for second indication

                  	 
      	
                    [**]

                  
	
                    8.

                  	
                    File
      NDA in U.S. for second indication

                  	 
      	
                    [**]

                  
	
                    9.

                  	
                    File
      for approval of Licensed
      Product in Europe for second indication

                  	 
      	
                    [**]

                  
	
                    10.

                  	
                    File
      for approval of Licensed
      Product in Japan for second indication

                  	 
      	
                    [**]

                  


          

        

      

    

     

    
      	
              4)

            	
              Within
      thirty (30) days of the execution of this Sixth Amendment, Licensee shall pay PHS an amendment issue
      royalty in the sum of One Hundred Thousand US Dollars ($100,000), to be
      sent to the address specified in Attachment
1.

            


    

     

    
      	
              5)

            	
              In
      the event any provision(s) of the Agreement is/are
      inconsistent with Attachment 1, such provision(s) is/are hereby amended to
      the extent required to avoid such inconsistency and to give effect to the
      shipping and payment information in such Attachment
  1.

            


    

     

    
      	
              6)

            	
              All
      terms and conditions of the Agreement not herein
      amended remain binding and in
effect.

            


    

     

    
      	
              7)

            	
              The
      terms and conditions of this Amendment shall, at
      PHS' sole option,
      be considered by PHS to be withdrawn from
      Licensee's
      consideration and the terms and conditions of this Amendment, and the Amendment itself to be
      null and void, unless this Amendment is executed by
      the Licensee and a
      fully executed original is received by PHS within sixty (60)
      days from the date of PHS signature found at
      the Signature Page.

            


    

     

    
      	
              8)

            	
              This
      Sixth Amendment is
      effective upon execution by all
parties.

            


    

     

     

    SIGNATURES
BEGIN ON NEXT PAGE

     

     

    
      	
              A-285-2009

            	 
      	
              CONFIDENTIAL

            
	
              Sixth
      Amendment of L-354-1998/0

            	
              Final
      REPROS THERAPEUTICS, INC.

            	
              July
      7, 2009

            
	
              Model
      09-2006 (updated 3-2009)

            	
              Page 2
      of 5

            	
              L-354-1998/6

            


      


      __________________

      Portions
of this Exhibit have been omitted pursuant to a request for confidential
treatment pursuant to Rule 24b-2 under the Securities Exchange Act of 1934,
as amended, and Rule 406 under the Securities Act of 1933, as amended.
These omitted portions have been marked with "**" and have been filed separately
with the Securities and Exchange Commission.

    

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    SIGNATURE
PAGE

     

    In
Witness Whereof, the parties have executed this Sixth Amendment on the dates
set forth, below. Any communication or notice to be given shall be forwarded to
the respective addresses listed below.

     

    
      
        
          	
                  For
      PHS:

                   

                  /s/  Mark L.
      Rohrbaugh

                  Mark
      L. Rohrbaugh, Ph.D., J.D.

                  Director

                  Office
      of Technology Transfer

                  National
      Institutes of Health

                   

                  Mailing
      Address for Agreement
      notices:

                  Chief,
      Monitoring & Enforcement Branch, DTDT

                  Office
      of Technology Transfer

                  National
      Institutes of Health

                  6011
      Executive Boulevard, Suite 325

                  Rockville,
      Maryland 20852-3804 U.S.A.

                	
                   

                   

                  7/7/09

                  Date

                
	 
      	 
      


        

      

    

    For Licensee (Upon, information
and belief, the undersigned expressly certifies or affirms that the contents of
any statements of
Licensee made or referred to in this document are truthful and
accurate.):

     

    
      
        
          	
                  by:

                  /s/  Joseph S.
      Podolski

                  Joseph
      S. Podolski

                  Chief
      Executive Officer

                   

                  Official
      and Mailing Address for Agreement
      notices:

                  Joseph
      S. Podolski

                  Chief
      Executive Officer

                  Repros
      Therapeutics, Inc.

                  2408
      Timberloch Place

                  Suite
      B-7

                  The
      Woodlands, Texas 77380

                  Email
      Address:

                  Telephone:

                  Fax:

                	
                   

                  7/7/09

                  Date

                
	 
      	 
      


        

      

    

     

    
      	
              A-285-2009

            	 
      	
              CONFIDENTIAL

            
	
              Sixth
      Amendment of L-354-1998/0

            	
              Final
      REPROS THERAPEUTICS, INC.

            	
              July
      7, 2009

            
	
              Model
      09-2006 (updated 3-2009)

            	
              Page 3
      of 5

            	
              L-354-1998/6

            


    

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    Official
and Mailing Address for Financial notices (Licensee's contact person
for royalty payments):

     

    Louis
Ploth

    CFO and
VP, Business Development

    Repros
Therapeutics, Inc.

    2408
Timberloch Place

    Suite B-7

    The
Woodlands, Texas 77380

    Email
Address:

    Telephone:

    Fax:

     

    Any false
or misleading statements made, presented, or submitted to the Government, including any
relevant omissions, under this
Agreement and during the course of negotiation of this Agreement are subject to all
applicable civil and criminal statutes including Federal statutes 31 U.S.C.
§§3801-3812 (civil liability) and 18 U.S.C. §1001 (criminal liability
including fine(s) or imprisonment).

     

     

    
      	
              A-285-2009

            	 
      	
              CONFIDENTIAL

            
	
              Sixth
      Amendment of L-354-1998/0

            	
              Final
      REPROS THERAPEUTICS, INC.

            	
              July
      7, 2009

            
	
              Model
      09-2006 (updated 3-2009)

            	
              Page 4
      of 5

            	
              L-354-1998/6

            


    

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    ATTACHMENT 1 — ROYALTY
PAYMENT OPTIONS

     

    NIH/PHS License
Agreements

     

    *In order to process payment
via Electronic Funds Transfer sender MUST supply the following
information:

     

    Procedure
for Transfer of Electronic Funds to NIH for Royalty Payments

     

    Bank
Name:

     

    NOTE:  Only
U.S. banks can wire directly to the Federal Reserve Bank, Foreign banks cannot
wire directly to the Federal Reserve Bank, but must go through an intermediary
U.S. bank. Foreign banks may send the wire transfer to the U.S. bank of their
choice, who, in turn forwards the wire transfer to the Federal Reserve
Bank.

     

    Checks
drawn on a U.S. bank account should be sent directly to the following
address:

     

    National
Institutes of Health (NIH)

     

    Overnight
or courier deliveries should be sent to the following address:

     

    Checks
drawn on a foreign bank account should be sent directly to the following
address:

     

    National
Institutes of Health (NIH)

    Office of
Technology Transfer

    Royalties
Administration Unit

     

    All
checks should be made payable to "NIH Patent Licensing."

     

    The OTT Reference Number
MUST appear on checks, reports and correspondence

     

     

     

    
      	
              A-285-2009

            	 
      	
              CONFIDENTIAL

            
	
              Sixth
      Amendment of L-354-1998/0

            	
              Final
      REPROS THERAPEUTICS, INC.

            	
              July
      7, 2009

            
	
              Model
      09-2006 (updated 3-2009)

            	
              Page 5
      of 5

            	
              L-354-1998/6